Dental caries is a demineralization of the tooth surface caused by oral bacteria present thereon. Specifically, organic acid produced by the oral bacteria is prevented from being diffused by some obstructions and the teeth are exposed to a high concentration of the organic acid, so that the tooth surface is demineralized. In this definition, any oral bacteria having the ability to ferment sugar to produce organic acid by metabolism can cause dental caries. Substrates suitable for organic acid production are saccharides, including monosaccharides and oligosaccharides (e.g., glucose and sucrose), and polysaccharides (e.g., starch) which are polymers of monosaccharides.
The dispersion of organic acid is prevented roughly due to (1) retention of starch taken from diet at the neck and root of tooth, and (2) adhesion of insoluble glucan to tooth, which is produced by bacteria using easily degradable sugars, such as sucrose (i.e., fermentative sugars) as substrates.
As to factor (1), any oral bacteria having the ability to ferment sugar, such as lactobacillus, is considered to be responsible for dental caries. In this case, it is known that the progression of dental caries is generally slow. The development of an environment in which a high concentration of organic acid is produced depends on passive factors.
Factor (2) is a major factor for dental caries today when sucrose-containing foods are widely available. In this case, Streptococcus mutans and Streptococcus sobrinus are believed to be causative. Both bacteria are a type of Streptococcus which occurs in chains, each cell having a diameter of about 0.6 μm in a round form. Both bacteria vigorously produce water-insoluble α-glucan in the presence of sucrose. This glucan has a property to adhere very well to the tooth surface. The bacteria rapidly metabolize sucrose, exerting the ability to produce acid. The bacteria per se have strong acid resistance and can survive in an acid environment in which other bacteria cannot grow. The adhesiveness of the water-insoluble glucan allows the bacteria to be firmly adhered to the tooth surface and the like. The water-insoluble glucan adsorbed to the tooth surface prevents the dispersion of organic acid produced by the bacteria, resulting in an environment in which the tooth surface is exposed to a high concentration of organic acid. It is considered that as compared to factor (1), the creation of the environment in which a high concentration of organic acid is produced depends on an active factor of the bacteria. In this case, the progression of dental caries is faster than that caused by factor (1).
There is a new approach to prevent dental caries by considering the health of teeth at microscopic levels, i.e., demineralization and remineralization of dentin (Yoichi Iijima, Takashi Kumagaya; Kariesu Kontororu Dakkai-to Saisekkaika-no-Mekanizumu [Caries Control—Mechanism of Demineralization and Remineralization], Ishiyaku Shuppan K.K.; 21-51, 1999). The surface of a tooth is made of calcium and hydroxyapatite [Ca10(PO4)6(OH)2] which is a crystal of phosphate, and is called enamel. Enamel is the hardest part of a tooth, and prevents important calcium or phosphate from being dissolved from underneath the enamel (demineralization) due to organic acid produced by bacteria in dental plaque, acid contained in foods, etc.
The organic acid permeates enamel through gaps between enamel rods which are filled with water, and dissolves hydroxyapatite by a process called demineralization. A loss of calcium and phosphate from enamel tissues leads to the development of initial dental caries under the surface layer of enamel. As described below, according to the present invention, dental caries in the above-described stage can be repaired. Calcium and phosphate ions permeate the dental caries portion under the enamel surface and lost apatite can be restored by a process called remineralization.
Each time that the diet containing fermentative carbohydrates is taken in, the pH of plaque becomes acidic and exceeds a critical pH at which demineralization begins. This results from the action of acid-producing bacteria in the plaque. When the plaque is buffered by saliva, the pH of the plaque is returned to neutral, and calcium and phosphate ions in saliva are reincorporated into dentin through the plaque (this process is called remineralization).
Therefore, means for preventing and treating tooth decay should not be a nutrient for oral bacteria which cause dental caries to allow the bacteria to produce organic acid; should not be a nutrient for mutans bacteria which cause dental caries to allow the bacteria to produce water-insoluble glucan and organic acid; should prevent pH reduction due to the organic acid from going below the pH at which demineralization begins (e.g., should have a buffering ability so as to prevent the pH reduction); should promote remineralization; and the like.
To date various anti-dental caries agents have been known.
Dental caries begin when mutans bacteria produce water-insoluble glucan using sucrose as a nutrient and glycosyltransferase as an enzyme. This glucan covers the tooth surface, resulting in dental plaque. When the mutans bacteria undergo acid fermentation within the dental plaque, the teeth is dissolved away and tooth decay is formed.
As anti-dental caries saccharides, some oligosaccharides which are not a nutrient for mutans bacteria have already been proposed (S. Hamada et al., J. Jpn. Soc. Starch Sci., Vol. 31, pp. 83-91, 1984). One example of these anti-dental caries saccharides is palatinit (Japanese Laid-Open Publication No. 2000-281550). When palatinit is combined with fluorine or zinc, the remineralization of teeth is promoted (Japanese Laid-Open Publication No. 2000-247852). However, palatinit has poor sweetness and is not preferable for foods. Further, a concentration of as high as about 1 to 20 wt % is required for the remineralization effect of palatinit.
Sugaralcohol (particularly, xylitol) is also known as an anti-dental caries agent (e.g., Japanese Laid-Open Publication No. 2000-128752 and Japanese Laid-Open Publication No. 2000-53549). Japanese Laid-Open Publication No. 11-12143 discloses an oral composition comprising one or more sugar alcohols selected from xylitol, mannitol, galactitol, and inositol. Japanese Laid-Open Publication No. 11-12143 describes that these sugar alcohols can promote the remineralization of teeth, but do not inhibit the growth of the bacteria. Although sugar alcohol is effective only at high concentrations, it is known that the intake of the sugar alcohol in a large amount causes loose stool. As described in the Examples below, the effect of xylitol was not substantially confirmed.
Further, polyphenol which is a component of tea has been reported and utilized as an anti-dental caries agent (S. Sakanaka et al., Fragrance Journal, Vol. 11, pp. 42-49, 1990). However, use of polyphenol also causes a problem with taste and is therefore limited.
At present, fluorine is said to be most effective for the remineralization effect. Fluorine can exert sufficient efficacy at about 2 ppm. In regard to the efficacy of fluorine, the following two points have been clarified: (1) promotion of remineralization; and (2) fluorine is incorporated into a hydroxyapatite crystal which is in turn converted to a hard crystal structure which resist demineralization (fluorine is used in expectation of effect (2) rather than (1)). Fluorine having such properties has been recently added to various oral compositions. For example, Japanese Laid-Open Publication No. 11-130643 discloses an oral composition containing calcium carbonate and a soluble fluoride compound. It is known that a combination of fluoride ions with sugar alcohol enhances the ability of fluorine to remineralize teeth (For example, Japanese Laid-Open Publication No. 11-21217, Japanese Laid-Open Publication No. 2000-72638, and Japanese Laid-Open Publication No. 2000-154127). Japanese Laid-Open Publication No. 8-12541 discloses a composition containing mutanase and a fluoride compound, which enhances dentin and promotes remineralization to effectively prevent dental caries.
It is known in the art that supply of calcium phosphate promotes the remineralization of teeth (e.g., Japanese Laid-Open Publication No. 11-228369 and Japanese Laid-Open Publication No. 10-310513).
Japanese Laid-Open Publication No. 11-29454 discloses an oral composition containing calcium carbonate and alginate. This composition enhances the ability of calcium carbonate to adhere and remain on teeth so that satisfactory naturalization of pH and promotion of remineralization are obtained, resulting in an excellent dental caries-preventing effect.
Japanese Laid-Open Publication No. 8-104696 describes that phosphorylated oligosaccharides disclosed therein suppress calcium and phosporus from being deposited and crystallized (i.e., calcification), that the phosphorylated oligosaccharides are not a nutrient for mutans bacteria which cause dental caries so that water-insoluble glucan is not produced, and that the phosphorylated oligosaccharides have a buffering ability and have the effect of preventing pH reduction. The above-described properties prevent the development of dental calculus and dental plaque, and the acid fermentation by mutans bacteria. It is also disclosed that phosphorylated oligosaccharides contained in a dietary composition or an oral composition have the effect of preventing pH reduction due to lactic acid, which is a product of fermentation within dental plaque, without an influence on flavor. However, Japanese Laid-Open Publication No. 8-104696 does not suggest that the above-described phosphorylated oligosaccharides can have the remineralization effect at a low concentration as described herein.